Dextro-rotary glaucine or d-glaucine hydrobromide has been used as an antitussive agent. D-glaucine can be isolated from the yellow poppy. The racemate, d,l-glaucine can be synthesized from papaverine, following the procedure of Frank and Tietze, Angewandte Chemie (1967) pp 815-6, or Helm, Belgian Pat. No. 866,079, and the racemate can be resolved with d-tartaric acid as disclosed by the above mentioned Helm Belgian patent. A variety of other preparative procedures are also known. Cham and Maitland, J. Org. Chem. J. Chem. Soc. (C) 1966, 753; and Cava, et al. J. Org. Chem. 35, 175 (1970). Separation of the isomers has been carried out by conventional procedures, such as using d- or l-tartaric acid to form the d- or l-bitartrate salts and separating the salts by fractional crystallization.
Glaucine has the structure ##STR1## and is thus structurally related to other plant alkaloids such as codeine and aporphine.
Codeine, and the related compounds such as hydrocodone, dihydrocodeine and dextromethorphan are well known as antitussive agents. Merck Index, Ninth Ed., Merck & Co., Rahway, N.J. (1976) monographs Nos. 2420-24, 3148, 4672, and 7908. Although these compounds, particularly codeine, are also well known to have a high potential for habituation or addiction, they are widely used, and codeine remains the most potent and widely used antitussive agents despite its abuse potential and other side effects. Codeine, hydrocodone, and dihydrocodeine have also been used as narcotic analgesics.
Antitussive agents are usually administered orally, most typically in the form of a liquid formulation such as an elixir, suspension or syrup, or in a solid lozenge or cough drop which is held in the mouth until it dissolves. In both cases the unpleasant bitter flavor of the alkaloid is known disadvantage of such agents. Various formulations have been developed to mask the unpleasant taste and after taste of codeine, dihydrocodeine and dextromethorphan, with varying degrees of success. None of these techniques have been completely successful. Glaucine, like codeine, has an unpleasant bitter taste.